Danta (1975) reported carpal tunnel syndrome (constrictive median neuropathy) in 4 persons in 3 generations with male-to-male transmission. Symptoms began in the first decade in father and son, and in both the median nerve at operation was found ... Danta (1975) reported carpal tunnel syndrome (constrictive median neuropathy) in 4 persons in 3 generations with male-to-male transmission. Symptoms began in the first decade in father and son, and in both the median nerve at operation was found to be constricted under a thickened transverse carpal ligament. Carpal tunnel syndrome has been described in amyloid neuropathy (see 176300) and in mucopolysaccharidoses (e.g., 253200) and mucolipidoses (252600). Gray et al. (1979) described bilateral carpal tunnel syndrome in 19 of 43 living members of a nonconsanguineous family, with male-to-male transmission. Sixty-three percent of the affected persons also had symptomatic digital flexor tenosynovitis, often polytendinous, which required surgery in 4. Age of onset was most often in the twenties but was at age 10 in 1 patient. Vallat and Dunoyer (1979) reported carpal tunnel syndrome in father and daughter. Kishi et al. (1975) and Kishi and Folkers (1976) used the level of erythrocyte glutamic oxaloacetic transaminase (EGOT) as a measure of vitamin B6 deficiency. Ellis et al. (1977) demonstrated severe deficiency of B6 in CTS. Administration of pyridoxine corrected the B6 deficiency and alleviated the neurologic disorder (Ellis et al., 1979). Further documentation of the improvement, which may obviate surgery, was presented by Ellis et al. (1982). They concluded that, since K(m) values of EGOT were identical in patients with and without CTS but with identical specific activities, CTS is a primary deficiency of B6, not a dependency state. Serratrice et al. (1985) described familial occurrence and onset at an early age (before 12 years) especially in the right hand (see also Lettin, 1965). McDonnell et al. (1987) described 5 definite and 3 possible cases of carpal tunnel syndrome in 3 generations of a family. A remarkable feature was the development of symptoms as early as age 4 years. Swoboda et al. (1998) described the case of a 7-month-old son of consanguineous Indian parents who presented with the recurrent chewing of his fingers in a median nerve distribution as the primary manifestation of carpal tunnel syndrome, in conjunction with features consistent with congenital insensitivity to pain. Electromyography (EMG) demonstrated severe median nerve entrapment at the wrist bilaterally, but other nerves were normal. In spite of clinical evidence of diffuse pain insensitivity, sural nerve and skin biopsies were normal, and he had no evidence of autonomic dysfunction. Hand findings evolved with scarring and infection of median innervated digits and loss of fine motor skills. Carpal tunnel release resulted in complete clinical resolution and significant EMG improvement. Milder symptoms and EMG evidence of median nerve entrapment were demonstrated in both parents, paternal grandparents, and several of his father's sibs. Swoboda et al. (1998) suggested that the child was homozygous for a mutant allele that in its heterozygous state predisposed to familial autosomal dominant carpal tunnel syndrome. Homozygosity for this or another mutant allele may have been responsible for his congenital insensitivity to pain. Stoll and Maitrot (1998) studied the family of an otherwise healthy 35-year-old woman with carpal tunnel syndrome and found that 7 other members of the family in 4 generations were affected. Only 2 of the 8 were male. None of the secondary causes of carpal tunnel syndrome, such as amyloidosis, were found in the family. Gossett and Chance (1998) reviewed reports of families with familial carpal tunnel syndrome and the guidelines used for the diagnosis. They identified 7 new 'potential' familial CTS pedigrees on the basis of their having 4 or more members with symptoms. In all but 2 pedigrees, however, an explanation other than familial CTS was found. Gossett and Chance (1998) concluded that familial isolated CTS is a rare, but genetically distinct disorder.
Elstner et al. (2006) reported a large family in which 9 members over 3 generations had bilateral carpal tunnel syndrome. The pedigree was compatible with autosomal dominant inheritance, but there was some evidence for an X-linked dominant transmission ... Elstner et al. (2006) reported a large family in which 9 members over 3 generations had bilateral carpal tunnel syndrome. The pedigree was compatible with autosomal dominant inheritance, but there was some evidence for an X-linked dominant transmission that was lethal in the hemizygous male: there was an almost exclusive occurrence of CTS in females, a preponderance of female to male offspring, and several male miscarriages. The affected matriarch had 6 sisters, no brother, 5 daughters, and 2 male miscarriages. The phenotype in this pedigree was consistent with anticipation, since the onset of CTS was approximately 20 years earlier in the third generation than in the second. Elstner et al. (2006) analyzed the peripheral myelin protein-22 (PMP22; 601097) and transthyretin (TTR; 176300) genes but found no alterations in affected family members; and linkage to the connexin-32 (GJB1; 304040) locus was excluded by haplotype analysis. Murakami et al. (1994) studied 2 sibs from a Japanese family with carpal tunnel syndrome. At the time of surgical carpal tunnel release, Congo-red stained biopsy material was obtained demonstrating the presence of amyloid. There were no other neurologic abnormalities, no orthostatic hypotension, no gastrointestinal problems or sphincter disturbances, and no vitreous opacities. The father, who had had symptoms of carpal tunnel syndrome, died at the age of 76 of pneumonia. In the sibs a tyr114-to-his substitution in transthyretin was detected (176300.0033).